One of the factors most clearly associated with the risk of cardio vascular disease is an elevated level of serum cholesterol particularly when associated with an inappropriate ratio of low density to high density lipo-protein. Intervention to reduce serum cholesterol levels is generally considered prudent medical practice. Unfortunately endogenous production of cholesterol is both considerable and stubbornly regulated and thus even severe dietary restriction has at best a limited effect. There has been therefore a considerable search for agents which suppress or limit endogenous production of cholesterol. One of the first of these discovered was triparinol which proved to be quite toxic and moreover blocked the biosynthesis of cholesterol at a rather late stage leading to accumulation of other sterol intermediates. These intermediates proved to be as unwelcome as cholesterol itself. It will be appreciated that there are many stages in conversion of acetate into cholesterol or precursor sterols, but it is well known that biochemical regulation of endogenous cholesterol synthesis is accomplished through a rather long feedback loop in which the product, cholesterol, inhibits further synthesis at the stage of the conversion of hydroxymethyl glutarate into mevalonate. Pharmacological intervention at this stage would therefore seem quite appropriate. It is now well known that 25 hydroxy cholesterol is a much more potent inhibitor of mevalonate synthesis than cholesterol itself, but large doses are still required for a pharmacological effect with unacceptable toxic side effects. Other exogenous agents which block the synthesis of mevalonate and thus cholesterol, notably the natural product compactin, have been found but in all cases the effect is either rather small or associated with toxicity.